The ATP-Binding Cassette Transporter BCRP1/ABCG2 Plays a Pivotal Role in Cardiac Repair After Myocardial Infarction Via Modulation of Microvascular Endothelial Cell Survival and Function

Higashikuni, Yasutomi; Sainz, Julie; Nakamura, Kazuto; Takaoka, Minoru; Enomoto, Soichiro; Iwata, Hiroshi; Sahara, Makoto; Tanaka, Kimie; Koibuchi, Nobutaka; Ito, Sumito; Kusuhara, Hiroyuki; Sugiyama, Yuichi; Hirata, Yasunobu; Nagai, Ryozo; Sata, Masataka

doi:10.1161/atvbaha.110.211755

Cited by 44 publications

(65 citation statements)

References 31 publications

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“…17 MI was induced in 8-to 12-week-old male C57BL/6 mice (Japan SLC, Shizuoka, Japan) by a permanent left anterior descending artery ligation as described previously with minor modification. 18 Briefly, mice were anesthetized by intraperitoneal injection of sodium pentobarbital (50 mg kg -1 of body weight). A 24-gauge polyethylene tube was inserted into the trachea and mechanical ventilation was provided by a rodent ventilator (Model SAR-830; CWE, Ardmore, PA, USA).…”

Section: Experimental Model Of MImentioning

confidence: 99%

“…For hemodynamic measurement, the right carotid artery was cannulated by the micro pressure transducers with an outer diameter of 0.42 mm (Samba 201 and Samba Preclin 420 LP; Samba Sensors AB, Vastra Frolunda, Sweden), which was then advanced into the LV. 18 Pressure signals …”

Section: Echocardiographic and Hemodynamic Measurementsmentioning

confidence: 99%

“…Infarct size was calculated as the sum of the endocardial and epicardial scar length divided by the sum of the LV endocardial and epicardial circumferences of all the sections. 18 …”

Section: Histological Analysismentioning

confidence: 99%

“…Reverse transcription was performed with 1 mg of total RNA, random hexamer primers and moloney murine leukemia virus (MMLV) reverse transcriptase (ReverTraAce-a; TOYOBO, Osaka, Japan). 18 For quantitative assessment of gene expression levels, quantitative real-time PCR analysis was performed. Specific mRNAs were quantified by SYBR Green real-time PCR Master Mix (TOYOBO) in an ABI PRISM 7000 thermocycler (Applied Biosystems, Foster City, CA, USA) under standard manufacturer's conditions.…”

Section: Rna Extraction and Reverse Transcriptase-pcr Analysismentioning

confidence: 99%

“…18 In lipid peroxidation assay, we measured concentrations of malondialdehyde and 4-hydroxyalkenals.…”

Section: Assessment Of Oxidative Stress In Murine Heartmentioning

confidence: 99%

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Aliskiren in combination with valsartan exerts synergistic protective effects against ventricular remodeling after myocardial infarction in mice

et al. 2011

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The efficacy of aliskiren, a direct renin inhibitor, in ventricular remodeling after myocardial infarction (MI) compared with conventional renin-angiotensin system (RAS) inhibitors remains to be defined. This study was performed to examine the protective effects of aliskiren and its addition to valsartan, an angiotensin-II receptor blocker, against ventricular remodeling after MI. MI was induced in 8-to 12-week-old C57BL/6 mice by ligating the left anterior descending artery. At 3 days after MI, mice were divided into five groups and were treated with the following: (1) phosphate-buffered saline (PBS); (2) hydralazine (10 mg kg -1 day -1 ); (3) valsartan (8 mg kg -1 day -1 ); (4) aliskiren (25 mg kg -1 day -1 ); and (5) combined aliskiren (25 mg kg -1 day -1 ) and valsartan (8 mg kg -1 day -1 ). With these doses of drugs, blood pressure-lowering effects compared with the PBS group were similar among the treated groups in sham-operated mice. At 28 days after MI, echocardiographic, hemodynamic and histological assessments demonstrated that monotherapy with valsartan or aliskiren alone significantly and similarly ameliorated ventricular remodeling after MI compared with the PBS and the hydralazine groups. Combination therapy of valsartan and aliskiren more greatly improved ventricular remodeling after MI with enhancement of angiogenesis and greater attenuation of tissue oxidative stress and inflammation. Our results indicate that aliskiren can be an alternative to conventional RAS inhibitors in the treatment of post-MI patients. Moreover, the dual therapy of valsartan and aliskiren may be more beneficial than either monotherapy. Further clinical trials will be warranted to sufficiently assess the safety and the efficacy of the use of aliskiren in post-MI patients.

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Section: Experimental Model Of MImentioning

confidence: 99%

Section: Echocardiographic and Hemodynamic Measurementsmentioning

confidence: 99%

“…Infarct size was calculated as the sum of the endocardial and epicardial scar length divided by the sum of the LV endocardial and epicardial circumferences of all the sections. 18 …”

Section: Histological Analysismentioning

confidence: 99%

Section: Rna Extraction and Reverse Transcriptase-pcr Analysismentioning

confidence: 99%

“…18 In lipid peroxidation assay, we measured concentrations of malondialdehyde and 4-hydroxyalkenals.…”

Section: Assessment Of Oxidative Stress In Murine Heartmentioning

confidence: 99%

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Aliskiren in combination with valsartan exerts synergistic protective effects against ventricular remodeling after myocardial infarction in mice

et al. 2011

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Designing Biomaterial Platforms for Cardiac Tissue and Disease Modeling

House¹,

Atalla²,

Lee³

et al. 2020

Advanced NanoBiomed Research

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Heart disease is one of the leading causes of death in the world. There is a growing demand for in vitro cardiac models that can recapitulate the complex physiology of the cardiac tissue. These cardiac models can provide a platform to better understand the underlying mechanisms of cardiac development and disease and aid in developing novel treatment alternatives and platforms toward personalized medicine. Herein, a summary of engineered cardiac platforms is presented. Basic design considerations for replicating the heart's microenvironment are discussed considering the anatomy of the heart. This is followed by a detailed summary of the currently available biomaterial platforms for modeling the heart tissue in vitro. These in vitro models include 2D surface modified structures, 3D molded structures, porous scaffolds, electrospun scaffolds, bioprinted structures, and heart‐on‐a‐chip devices. The challenges faced by current models and the future directions of in vitro cardiac models are also discussed. Engineered in vitro tissue models utilizing patients’ own cells can potentially revolutionize the way we develop treatment and diagnostic alternatives.

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Abcg2 Expression Marks Tissue-Specific Stem Cells in Multiple Organs in a Mouse Progeny Tracking Model

2012

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The side population (SP) phenotype is associated with the Hoechst dye efflux activity of the Abcg2 transporter and identifies hematopoietic stem cells (HSCs) in the bone marrow. This association suggests the direct use of Abcg2 expression to identify adult stem cells in various other organs. We have generated a lineage tracing mouse model based on an allele that co-expresses both Abcg2 and a CreERT2 expression cassette. By crossing these mice with lox-STOP-lox reporter lines (LacZ or YFP), cells that express Abcg2 and their progeny were identified following treatment with tamoxifen (Tam). In the liver and kidney, in which mature cells express Abcg2, reporter gene expression verified the expected physiologic expression pattern of the recombinant allele. Long term marking of HSCs was seen in multiple peripheral blood lineages from adult mice, demonstrating that Abcg2+ bone marrow HSCs contribute to steady state hematopoiesis. Stem cell tracing patterns were seen in the small intestine and in seminiferous tubules in the testis twenty months after Tam treatment, proving that stem cells from these organs express Abcg2. Interstitial cells from skeletal and cardiac muscle were labeled and some cells co-stained with endothelial markers, raising the question as to whether these may function as tissue-specific muscle stem cells. Altogether, these studies prove that Abcg2 is a stem cell marker for blood, small intestine, and testicular germ cells and provide a new model for studying stem cell activity that does not require transplant-based assays.

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The ATP-Binding Cassette Transporter BCRP1/ABCG2 Plays a Pivotal Role in Cardiac Repair After Myocardial Infarction Via Modulation of Microvascular Endothelial Cell Survival and Function

Cited by 44 publications

References 31 publications

Aliskiren in combination with valsartan exerts synergistic protective effects against ventricular remodeling after myocardial infarction in mice

Aliskiren in combination with valsartan exerts synergistic protective effects against ventricular remodeling after myocardial infarction in mice

Designing Biomaterial Platforms for Cardiac Tissue and Disease Modeling

Abcg2 Expression Marks Tissue-Specific Stem Cells in Multiple Organs in a Mouse Progeny Tracking Model

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